Search Results (55,119)

Objective: Current knowledge surrounding the diagnosis and mechanisms that result in immune checkpoint inhibitor-associated diabetes (ICI-DM) remain to be fully defined. We present clinical vignettes of patients that have presented to our hospital to illustrate the heterogenous clinical profiles that patients with ICI-DM can experience. We also provide an update on ICI-DM, focusing on current and future perspectives and emerging therapies. Methods: We performed a retrospective review of the electronic records of five ICI-DM patients who presented to St. Vincent’s Hospital Melbourne between 2020 and 2024, with patients identified from the hospital endocrinology and oncology databases. We also performed a literature review via a PubMed search using the keywords “checkpoint inhibitors” and “diabetes” between the years 2015 and 2025 to allow us to collate a descriptive review on ICI-DM. Results: Our cases show some heterogeneity in presentation, with biochemical evidence of diabetic ketoacidosis (DKA) in 4/5 patients, presentation 18–253 days (median 47 days) from ICI commencement, HbA1c 59–78 mmol/mol (median 66 mmol/mol), and c-peptide 0.06–0.77 pmol/mL (median 0.09 pmol/mL). Islet autoantibodies were present in 4/5 cases and high-risk HLA alleles identified in 1/2 tested patients. The findings from our descriptive review support a similar heterogeneity in ICI-DM presentations. Inconsistent diagnostic criteria for ICI-DM were noted with low c-peptide being the most common biochemical presentation. Pancreatic volume is emerging as a useful predictive marker of ICI-DM development. We found no reports of the reversal of ICI-DM with immunosuppression in humans, although recent preclinical studies suggest that this approach is feasible. Conclusions: Diagnostic criteria should include new-onset hyperglycaemia with low paired c-peptide, and may be supported with T1DM-associated autoantibodies and evidence of pancreatic atrophy on imaging. Further research is needed in the realm of predicting ICI-DM and considering the role of immunosuppression as a treatment modality. Full article

This work focused on the identification of angiotensin I-converting enzyme (ACE) inhibitory peptides from royal jelly (RJ) proteins and elucidated their inhibition patterns and mechanisms. RJ proteins were analyzed for ACE inhibition potential using in silico tools, and suitable enzymes were selected for peptide release. Hydrolysis conditions were optimized using response surface methodology (RSM), and the resulting peptides were fractionated and purified. Mass spectrometry identified 57 peptides, with seven selected for synthesis based on scoring. IDFDF, DVNFR, and SFHRL showed the highest ACE inhibition, with IC₅₀ values of 16.9 μM, 42.5 μM, and 242.6 μM, respectively. Lineweaver–Burk plots revealed IDFDF as a competitive inhibitor, DVNFR as a non-competitive inhibitor, and SFHRL as a mixed inhibitor. Molecular docking indicated that peptide–ACE interactions were primarily mediated through hydrogen bonds and Zn(II) coordination. This work promotes the sustainable utilization of RJ and the development of ACE inhibitory peptides derived from food sources. Full article

Nanoparticles (NPs) have great potential for stimulating plant growth and development, reducing the negative impact of various types of stress on plants, and increasing the yield of agriculturally important crops. Metal oxide NPs (MONPs) have been shown to have a significant effect on the physiological and biochemical processes in plants, enhancing plant resilience. Among them, CuO, Mn_xO_x, and ZnO NPs are of particular interest because they contain elements essential for plant function. However, widespread use in agrochemistry and plant protection requires a preliminary risk assessment due to their potential phytotoxic effects. Phytotoxicity manifests through the development of oxidative stress, genotoxicity, and transcriptional disruption. A decrease in plant growth and photosynthesis, increased lipid peroxidation (LPO), and the accumulation of toxic NPs in plant tissues were also observed. Among the studied MONPs, CuO and ZnO NPs exhibit the greatest phytotoxic effects. However, the effects of MONPs are dose-dependent. Numerous studies have shown that MONPs can stimulate plant biometric parameters and productivity, as well as influence biochemical processes. MONPs have been shown to influence the functioning of the plant antioxidant system, manifested by modulating the content of reactive oxygen species (ROS), the activity of antioxidant enzymes (AOEs), and the regulation of signaling pathways mediated by ROS and reactive nitrogen species. Furthermore, MONPs influence the accumulation of proline and phenols in plant tissues. MONPs have a pronounced effect on the functioning of the plant photosynthetic apparatus, manifested by changes in pigment content, the activity of photosynthetic enzymes, and the functioning of photosystems. MONPs can improve nutrient absorption, regulate osmotic balance, and activate plant defense mechanisms. ZnO NPs are effective in mitigating salt stress. CuO and Mn_xO_x NPs have shown promise in mitigating biotic stress. Furthermore, these NPs were found to reduce the toxicity of heavy metals to plants. Overall, when used wisely, MONPs hold promise for enhancing the physiological, biochemical, and agronomic performance of crop plants under conditions of global climate change, effectively addressing food security issues. Full article

In petroleum drilling, conventional automatic drilling systems still rely heavily on manual intervention, which often leads to poor stability, limited multivariable coordination, and large fluctuations in drilling pressure. To address this problem, this study develops a hydraulic drawworks-based autodriller system with integrated power, drive, actuation, and control units, and establishes a mechanical-hydraulic-control co-simulation model for the coordinated regulation of drill-string hoisting speed and surface weight-on-bit (SWOB). Based on this platform, a dual-loop control framework is developed in which the inner loop uses linear active disturbance rejection control (LADRC) for rapid disturbance estimation and compensation, while the outer loop uses PID control for tracking regulation. Feedforward compensation is introduced to handle predictable load variation, and PSO-assisted fuzzy tuning is used to improve adaptability under varying operating conditions. Simulation results show that, compared with conventional cascaded PID control, the proposed controller reduces drawworks speed and SWOB overshoot by 12.5% and 40%, respectively, while the corresponding settling times are shortened by 1.805 s and 2.443 s. Prototype experiments on a scaled test platform further show that the proposed controller can be implemented on physical hardware and can maintain stable real-time regulation under laboratory conditions. These results support the feasibility of the proposed framework for coordinated hydraulic drawworks control under the simulated and laboratory-scale conditions considered in this study. Full article

The digital transformation has intensified demands for university teachers to develop technology-enhanced teaching competence, especially under China’s High-Quality Course initiative for blended learning excellence. While existing well-recognized frameworks (e.g., TPACK, DigCompEdu) provide valuable foundational guidance, they inadequately capture the dynamic, ecological processes through which teachers systematically reconstruct curricula and professional identities in blended contexts. This study addresses this gap by proposing an ecological model of competence development, building on the strengths of existing frameworks while capturing the dynamic interplay between teachers, technology, and blended environments. Using a qualitative multiple-case design, we conducted semi-structured interviews with six national recognized exemplary university English teachers. Data were analyzed via Braun & Clarke’s six-phase thematic analysis in MaxQDA. Findings reveal that technology-enhanced teaching competence comprises five co-evolving dimensions: Curriculum Empowerment (systematic course redesign), Role Transformation (shifting from lecturer to learning designer), Environment Integration (orchestrating online-offline spaces), Technology Application (selective tool use), and Competence Spanning (transferring expertise across contexts). These dimensions form an ecological system: when teachers redesign curricula, they simultaneously rethink their professional identities; when they adopt technologies, they reshape classroom environments; and when all four dimensions align, higher-order spanning competence emerges naturally. Theoretically, this ecological model advances beyond technology addition by illuminating relational mechanisms and emergent properties of competence. Practically, it informs a shift from fragmented tool-training to systemic faculty support architectures that honor the complexity of blended teaching transformation. Full article

Materials derived from renewable and recycled resources offer a promising route toward more sustainable thermoset composites. In this study, waste poly(ethylene terephthalate) (PET) was depolymerized by glycolysis with propylene glycol to obtain a glycolysate, and subsequently polycondensed with biobased propylene glycol, maleic anhydride, and trimethylolpropane diallyl ether to synthesize biobased UV-curable unsaturated polyester resin (UV-bUPR). The composites were prepared with acryloyl-modified Kraft lignin (K_rL-A) as a reactive bio-filler using a dual-curing approach, in which rapid UV curing was followed by thermal/redox post-curing to improve conversion and network homogeneity. The structure of the synthesized resin and composites was confirmed by FTIR and NMR spectroscopy. Mechanical properties were evaluated by tensile testing and hardness measurements, while morphology and fracture behavior were analyzed by scanning electron microscopy. The unmodified lignin decreased tensile performance due to limited compatibility with the polyester matrix and the formation of interfacial defects and agglomerates. In contrast, K_rL-A exhibited improved dispersion and stronger filler–matrix interactions, resulting in superior mechanical performance. The most pronounced effect of lignin modification was observed at 15 wt.% filler loading, where the tensile strength reached 27.83 MPa, compared with 13.91 MPa for the corresponding unmodified system. The developed composites also showed improved sustainability, assessed through the E-factor, due to the combined use of recycled PET and renewable lignin. Full article

Energy poverty, as an emerging form of poverty, is key to consolidating the achievements of poverty alleviation and is also an important cornerstone for promoting energy transformation, social equity, and people’s well-being. Based on data from the China Family Panel Studies (CFPS) for 2018 to 2022, we use the head of household’s subjective happiness to proxy for family happiness. Using a two-way fixed-effects model, we analyze the impact of energy poverty on family happiness and its mechanism from the theoretical and empirical aspects. The conclusions are as follows: (1) Energy poverty has a significant negative impact on family happiness, and the estimated results of instrumental variables after solving endogeneity are consistent. (2) Heterogeneity analysis finds that for families with relatively disadvantaged economic conditions, such as non-relatively poor families, urban families, and families with loans, energy poverty significantly reduces their happiness, which contradicts our conventional understanding. (3) Mechanism analysis shows that energy poverty affects income gaps, health status, and economic status, which in turn affect family happiness. The respective percentages coming from the mechanisms of income gap, health status, and economic status are 43.31%, 26.11%, and 9.55%. We directly link energy sustainability, a core area of sustainable development, with residents’ well-being. It fills the systematic research gap on how energy poverty affects household happiness and deepens our understanding of its underlying transmission mechanism. Furthermore, it enriches research on the implementation pathways of energy policy and common prosperity, broadens the boundaries of research in energy economy and social welfare, and provides important practical implications for advancing energy inclusion and rural revitalization within the sustainable development framework. Full article

This paper presents the development and implementation of a two-degree-of-freedom, model-based controller designed to enhance the efficiency and flexibility of a certain class of circuits used in thermo-hydraulic applications. The controller addresses significant challenges such as time-variable transport delays and actuator coupling, which are common in dynamic testing environments. By utilising a model-based control approach and the Smith predictor configuration, the proposed controller simultaneously tracks supply temperature and mass flow rate with improved performance compared to the proportional–integrative–derivative (PID) controller used in our laboratory. The system’s effectiveness is demonstrated through a virtual hydraulic complex model developed in the OpenModelica environment and experimental tests, following the implementation of the controller in the laboratory real-time control software. Both the simulation and experimental results indicate that the controller can closely follow pre-programmed temperature and flow rate waveforms while effectively rejecting disturbances, with an RMSE reduction of up to about 80% under the specific test protocol used in this work, making it suitable for applications required to deal with the above constrains, such as laboratory dynamic testing and thermo-mechanical and chemical process regulation. Full article

Inter-basin water transfer projects (IBWTPs) play a pivotal role in alleviating the spatiotemporal imbalances of water resources. However, their operation is exposed to multiple, highly interdependent safety risks that can significantly undermine system stability and water supply reliability. Existing studies predominantly focus on isolated risk factors or rely heavily on subjective data, which limits their ability to capture the complex interrelationships among risks and reveal their underlying propagation mechanisms. To address these limitations, this study proposes a novel risk correlation analysis framework that integrates Interpretive Structural Modeling (ISM) with copula functions. ISM is first employed as a preprocessing tool to structure expert knowledge and develop an initial risk correlation framework. It is then used to hierarchically organize the complex interrelationships among risks. Subsequently, copula functions are utilized to model nonlinear dependencies and tail behaviors among risk variables. This enables a quantitative assessment of correlation strengths and facilitates the construction of a risk topological network. An empirical case study is conducted based on the Middle Route of the South-to-North Water Diversion Project. The results reveal 13 significant correlations among six second-level risk categories. Natural risks (e.g., floods and geological hazards) are identified as the primary driving factors. They exhibit a strong positive correlation (0.6155) with engineering risks and serve as the most critical nodes for proactive risk prevention and control. Engineering risks function as central intermediary hubs in the risk transmission process, whereas water quality and economic risks are characterized as terminal endpoints. Furthermore, three principal risk propagation pathways are identified: (1) natural risks → engineering risks → economic risks; (2) natural risks → operational scheduling risks → social risks; and (3) engineering risks → water quality risks → economic risks. The resulting risk topological network demonstrates significant small-world properties, indicating highly efficient risk transmission within the system. Ultimately, this study provides a robust quantitative approach for analyzing risk interactions in complex engineering systems and enriches the theoretical framework of engineering risk management. It also identifies critical nodes and key transmission pathways for risk prevention and control in IBWTPs, thereby offering significant practical implications for operational safety. Full article

The management of plastic packaging waste needs to be optimized to improve recycling rates. In this article, fourteen categories of non-bottle polyethylene terephthalate (PET) packages were mechanically recycled at laboratory bench scale; the generated data were assessed using a multi-criteria decision analysis (MCDA) approach to identify the categories most suited for the mechanical recycling process from social, technical and legislative viewpoints. Recycling yields varied between 75% and 92% across the 14 categories. The intrinsic viscosity (IV) values of the produced recycled PET (rPET) corresponded to molecular weights ranging from 28,000 to 35,000 g/mol. The MCDA recyclability assessment showed that 7 of the 14 categories (accounting for 72% of the sorted products by mass flow) are often composed of multiple, inseparable materials, resulting in the lowest-quality rPET. Furthermore, only 4 categories (approximately 28% of the categories) were found suitable for closed-loop mechanical recycling. The stakeholders involved in the PET packaging value chain could use these results to support decision-making and the development of a well-organized framework to valorize even the most complex types of plastic waste. Full article

Island reef road construction faces a complex marine service environment characterized by high salinity and high humidity. Meanwhile, rapid construction and prompt subgrade repair are urgently required, creating a strong demand for novel calcareous-sand-based stabilization materials that combine excellent mechanical performance with resistance to seawater erosion. To this end, this study developed an early-strength cemented calcareous-sand reinforcement material for road base construction. Sulfoaluminate cement (SAC) and ferrite-aluminate cement (FAC), both featuring rapid setting/early strength development and superior corrosion resistance, were used to cement calcareous sand (CS) and to investigate its mechanical and microstructural characteristics under different water environments. Unconfined compressive strength tests (UCS) showed that SC-CS and FC-CS could meet subgrade requirements at 1 d and 7 d, with SC-CS and FC-CS reaching 3.12 MPa and 3.44 MPa at 1 d, and 3.26 MPa and 3.67 MPa at 7 d, respectively, under seawater SS conditions. Seawater mixing and immersion were found to promote the early strength and stiffness development of both SC-CS and FC-CS, with a more pronounced effect observed for FC-CS. Based on experimental results, a damage model for the stabilized specimens was established with a fitting accuracy of R² > 0.97. This constitutive model accurately describes the stress–strain relationship of the material and quantitatively characterizes its damage evolution. Microscopic XRD and SEM analyses indicated that the main hydration product in freshwater-cured specimens was ettringite, and the interparticle connection of CS was dominated by bridging through rod-like ettringite. In contrast, under seawater conditions, the ettringite content decreased, while hydrotalcite and calcium aluminate hydrate increased, forming massive and lamellar bridging products. Compared with SC-CS, the bridging structure in FC-CS was denser. Moreover, the compactness of the bridging structure not only affected its mechanical properties but also governed the movement mode of CS particles, thereby influencing the damage evolution and failure mode of the specimens. The findings provide theoretical support for the construction needs of island road. Full article

Hybrid gas separation technologies combining different physicochemical mechanisms represent a promising approach for the efficient treatment of complex natural gas mixtures. In this work, a hybrid process integrating gas hydrate crystallization and membrane gas separation was investigated for the upgrading of multicomponent natural gas-containing hydrocarbons (C₁–C₄), acid gases (CO₂ and H₂S), and inert components. Polysulfone hollow-fiber membranes were fabricated, and their gas transport properties were experimentally determined using an eight-component quasi-real natural gas mixture under elevated pressure conditions. The obtained mixed-gas permeance values were used as input parameters for the development of a detailed mathematical model of a hollow-fiber membrane module implemented in the Aspen Custom Modeler. The model was applied to simulate membrane separation of both gas- and hydrate-derived streams produced by the gas hydrate crystallizer. Simulation results were analyzed in terms of hydrocarbon composition, acid gas removal efficiency, and hydrocarbon recovery as a function of the stage-cut. The modeling predictions were validated experimentally using a laboratory membrane module integrated with the gas hydrate crystallization unit. Good agreement between the experimental data and simulation results was observed for all major components. The deviation between modeled and experimental concentrations remained small, while the discrepancy in hydrocarbon recovery was higher and reached approximately 10–20%, which is attributed to the cumulative uncertainty of flow rate and composition measurements. These results confirm the adequacy of the developed model. The hybrid process demonstrates strong complementarity between the thermodynamic selectivity of hydrate formation and the transport selectivity of membrane separation, enabling efficient removal of acid gases while maintaining acceptable hydrocarbon recovery. The results indicate that the proposed gas hydrate–membrane hybrid process is a promising strategy for advanced natural gas purification and upgrading. Full article

Background/Objectives: A central question in molecular genetics concerns how transcriptional regulatory sequences and de novo genes originate and reach evolutionary fixation. In this study, we utilize the human bicistronic gene SMIM45 as a model to analyze the evolutionary trajectories of gene development. This locus comprises several functional units: three enhancers (one featuring an embedded silencer), an exonic silencer that partially overlaps an ORF, a highly conserved ancestral sequence encoding a 68 aa microprotein, and a human-specific de novo gene encoding a 107 aa protein expressed spatiotemporally in embryonic brain tissues. Methods: The alignment of gene sequences from different species was used to determine the evolutionary development of enhancers and silencers, and the development of the exonic silencer was determined through application of the cultivator model and assessment of nearest-neighbor bases. Results: We identify significant disparities in formation mechanisms; for example, the LOC127896430 NANOG hESC enhancer originated simply via two Alu insertions that constitute the enhancer. In contrast, the exonic silencer (a segment of the LOC130067579 ATAC-STARR-seq lymphoblastoid silent region 13815)—a distinct, novel type of silencer—originated from a combination of diverse mechanisms, including a “cultivator gene” process of base pair fixation, consistent with the cultivator model proposed by Li Zhao and coworkers. Conclusions: SMIM45 exemplifies novel development mechanisms occurring over hundreds of millions of years, culminating in the birth of a human-specific, de novo 107 aa cistron. The associated complex of enhancers and silencers suggests intricate regulation of the 107 aa protein in fetal brain tissues. Full article

Airfoil fin Printed Circuit Heat Exchangers (PCHEs) offer significant advantages in reducing flow resistance, promoting turbulence, and enhancing heat transfer performance due to their discrete fin configuration. However, compared with conventional continuous-channel structures, the geometric discontinuities and sharp trailing edges introduced by discrete fins tend to induce severe stress concentration at the fin roots, resulting in a more complex structural response. In this study, a PCHE core with NACA0020 airfoil fins is investigated. Finite element analysis combined with a sequential one-way thermo-structural coupling approach is conducted to characterize the fins’ stress and deformation behavior under high temperature and pressure. The plate region is evaluated based on the linear elastic stress criteria specified in ASME Boiler and Pressure Vessel Code Section III, while localized yielding regions such as the fin roots are assessed using an equivalent plastic strain indicator. Results indicate that the structural response of the PCHE core is dominated by pressure loading under the investigated operating conditions with ΔT = 18 °C and ΔP = 12.05 MPa, whereas thermal stress caused by constrained thermal expansion mainly modifies local stress distributions and has a limited effect on global deformation. Owing to the discontinuous support provided by discrete airfoil fins, the fin roots act as the primary load-transfer path and sustain higher stress levels. The maximum von Mises stress is observed at the trailing edge of the fin root on the high-pressure side, while the largest deformation occurs in the unsupported plate region and is governed by bending. Parametric analysis indicates that, within the investigated parameter range, a fully staggered fin arrangement promotes more uniform load distribution and exhibits the most favorable structural response. In contrast, increasing the fin chord length and relative thickness reduces the overall load-carrying capacity of the core. Finally, a power-law predictive correlation for the maximum total plate deformation was developed, showing that the parameter influence on plate structural response follows the order horizontal pitch (L_h) > vertical pitch (L_v) > channel etching depth (L_e) > staggered pitch (L_s). In contrast, normalized sensitivity analysis of the maximum fin-root von Mises stress shows the order staggered pitch (L_s) > horizontal pitch (L_h) > vertical pitch (L_v) > channel etching depth (L_e), indicating that global plate deformation and local fin-root response are governed by different structural mechanisms. Full article

The construction sector consumes significant amounts of natural resources and contributes substantially to global CO₂ emissions, making it necessary to develop materials with a reduced environmental impact. In this context, the valorization of reusable industrial waste as secondary raw materials represents a strategic direction for applying circular economy principles and for decarbonizing the construction materials industry. The scientific problem addressed in this review is the urgent need to develop construction materials with a reduced environmental footprint, given that the construction sector is a major consumer of natural resources and a significant contributor to global CO₂ emissions. This challenge requires the identification and critical evaluation of sustainable solutions that support decarbonization and the transition toward a circular economy. The main findings indicate that the valorization of industrial waste offers high decarbonization potential: supplementary cementitious materials (SCMs), such as ground granulated blast furnace slag and fly ash, can reduce CO₂ emissions by approximately 20–50%, while alkali-activated binders and geopolymers achieve reductions of 40–80% compared to Portland cement. These materials also enhance durability, extending service life by 10–20% in aggressive environments, although early-age strength may decrease by 10–30%; recycled aggregates derived from construction and demolition waste (CDW) can substitute up to 100% of natural aggregates, while rubber fibers can increase impact resistance by 30–50% and reduce density by 10–20%. However, key limitations relate to waste variability, heavy metal leaching risks (requiring immobilization efficiencies > 90%), and the relatively low technological maturity of many solutions (TRL < 7), leading to the TRL–CO₂ paradox and highlighting the need for standardization and performance-based regulatory frameworks. The synthesized results indicate that the appropriate integration of industrial waste enables a significant reduction in clinker content, lowers associated CO₂ emissions, and decreases primary energy consumption while maintaining physical–mechanical properties and durability characteristics comparable to or in some cases superior to those of traditional materials, if mix design is based on clear performance criteria, stratified according to the type of waste, dosage used, curing regime, binder chemistry, and the target application. Full article